Egyptian Journal of Anaesthesia (2015) 31, 303–308

HO ST E D BYEgyptian Society of Anesthesiologists

Egyptian Journal of Anaesthesia

www.elsevier.com/locate/egjawww.sciencedirect.com

Research Article

Use of remifentanil in comparison with sodium

nitroprusside for controlled hypotension during

rhinoplasty: Randomized controlled trail

* Corresponding author at: Anesthesia and ICU Department, Faculty

of Medicine, Ain Shams University, Lotfy Alsaid Street Abassia,

Cairo, Egypt. Tel.: +20 1022604863.

Peer review under responsibility of Egyptian Society of Anesthesiol-

ogists.

http://dx.doi.org/10.1016/j.egja.2015.06.0031110-1849 ª 2015 Production and hosting by Elsevier B.V. on behalf of Egyptian Society of Anesthesiologists.

Eman Mohammed Kamal Aboseif *, Sameh Mohammed Osman

Anesthesia and ICU Department, Faculty of Medicine, Ain Shams University, Egypt

Received 28 February 2015; revised 26 May 2015; accepted 2 June 2015Available online 14 July 2015

KEYWORDS

Remifentanil;

Sodium nitroprusside;

Controlled hypotension;

Rhinoplasty

Abstract Objective: To evaluate the clinical efficacy of remifentanil infusion in comparison with

sodium nitroprusside regarding controlled hypotension during rhinoplasty.

Background: Controlled hypotension is a well-known technique used in many operations to reduce

blood loss and need for blood transfusion and to provide satisfactory bloodless surgical field. Many

pharmacological agents are used to perform controlled hypotension intraoperatively.

Patients and methods: A total of 130 adult consented patients of both sexes undergoing rhinoplasty

aged 20–45 years with ASA I or II, were randomized to receive remifentanil infusion

0.25–0.5 lg/kg/min (group I = 65 patients) or sodium nitroprusside 0.5 l/kg/min intraoperatively

with adjusting dose till reaching target MAP around 80 mmHg. Anesthetic technique was standard

for both groups. Time to onset of induced hypotension and time to target MAP were recorded in

addition to heart rate during induced hypotension, PaO2, PCO2 and PH together with the total

infusion dose of the hypotensive agents in both groups.

Results: Remifentanil infusion intraoperatively induces adequate hypotension with no statistical

significant difference to that induced by sodium nitroprusside (P < 0.05).

Conclusion: This study confirmed that remifentanil infusion with dose of 0.25–0.5 lg/kg/min.

induced desired controlled hypotension intraoperatively during rhinoplasty with no complications

occurred either intra- or postoperative with advantage of rapid recovery from anesthesia.ª 2015 Production and hosting by Elsevier B.V. on behalf of Egyptian Society of Anesthesiologists.

1. Introduction

Controlled hypotension has been used to reduce bleeding andthe need for blood transfusion, and also to provide a satisfac-

tory bloodless surgical field in many operations as in oromax-illofacial surgery, endoscopic sinus surgery, rhinoplasty,middle ear surgery, major orthopedic surgery (as hip or knee

Figure 2 Mean heart rate during induced hypotension in both

study groups.

304 E.M.K. Aboseif, S.M. Osman

replacement, spinal) cardiovascular, neurosurgery and livertransplant surgery [1].

Controlled hypotension is defined as a reduction of the sys-

tolic blood pressure to 80–90 mmHg, a reduction of mean arte-rial pressure (MAP) to 50–65 mmHg or a 30% reduction ofbaseline MAP [2]. Many pharmacological agents used for con-

trolled hypotension include those that can be used successfullyalone or in combination with others to limit dosage require-ments and the adverse effects of each agent [3]. The common

agents that had been used are inhalational anesthetics, sodiumnitroprusside, nitroglycerin, adenosine, prostaglandin E, betablockers (especially esmolol), calcium channel blockers andnacrcotics (especially remifentanil [4] (see Figs. 1–6).

Other agents may be used mainly as adjunctive as ACEinhibitors and a2 agonists (e.g. clonidine) [5]. The main goalof any hypotensive drug is to achieve the desired level of con-

trolled hypotension without affecting the perfusion of vitalorgans and should have a rapid onset, which is easy to beadministered and disappears quickly when administration is

discontinued without toxic metabolites [6]. The new ultra-short acting l-opioid receptor agonist (Remifentanil)hydrochloride is known to have a hypotensive effect during a

propofol total intravenous anesthesia = TIVA, and this isused effectively for controlled hypotension and providing aclear dry surgical field [7].

Sodium nitroprusside is a well-known direct vasodilator

(acting on both arterioles and venules) commonly used toinduce controlled hypotension with its high potency and shortduration of action but it has many side effects and disadvan-

tages making it is not suitable for many patients. Reboundhypertension and increased potentials for cyanide toxicity,and tachyarrhythmia are the common side effects [8].

The purpose of this study was to evaluate the effectivenessof remifentanil to induce controlled hypotension as primary

Figure 1 Mean time to onset of induced hypotension and time to

target blood pressure in both study groups.

Figure 3 Change in PaO2 in both study groups. Error bars

represent 95% CI.

Figure 4 Change in PaCO2 in both study groups. Error bars

represent 95% CI.

Figure 5 Change in pH in both study groups. Error bars

represent 95% CI.

Use of remifentanil in comparison with sodium nitroprusside for controlled hypotension 305

goal and to reduce the disadvantage of traditional methodsused to induce controlled hypotension as the secondary goal.

2. Patients and methods

After approval of the local ethical committee, a total of 130patients ASA I or II of both sexes with ages ranging from 20

to 45 years undergoing rhinoplasty were randomly dividedusing closed sealed envelope method of randomization intotwo groups remifentanil group (group I, n = 65 patients) or

sodium nitroprusside group (group II, n = 65 patients).Exclusion criteria were, patients with uncontrolled hyper-

tension, severe renal or hepatic diseases, anemia age <20

and >45 years, patients who refused to participate in this

Figure 6 Method done for the flowchart

study and patients with severe ischemic heart disease or cardiacfailure.

All patients were admitted on the day before surgery and

fasted for at least 8 h before surgery. All patients received pre-operative sedation in the form of midazolam (0.5 mg/kg) twohours before surgery.

In all patients, a 20-gauge catheter was inserted into the leftradial artery for direct determination of arterial blood pressure(systolic, mean, diastolic). Heart rate was continually recorded

by 5-lead ECG, also other routines were monitored in the formof pulse oximetry, and end tidal CO2 was connected. Serialarterial blood gas analysis was done to detect any changes inPH or in the partial pressures of Oxygen (PaO2) and carbon

dioxide (PaCO2). Samples were taken every 30 min after theinduction of general anesthesia until 20 min in the recoveryroom.

An 18-gauge cannula was inserted into a suitable vein forfluid and drug administration: Ringer’s solution was adminis-tered continuously at a rate of 5 ml/kg/h.

3. Anesthetic technique

– In all cases, induction was done by 2 mg kg�1 propofolfollowed by rocurorium 0.6 mg/kg to facilitate oro-

tracheal intubation by cuffed tubes, then the patientswere connected to the mechanical ventilator to maintainan end tidal CO2 ranging from 30 to 35 mmHg and to

ensure SpO2 P 97% with 50% N2O in oxygen.Anesthesia was maintained by Sevoflurane with MAC1.5–2% and with increments of the muscle relaxant

(rocurorium) every 40 min (=0.15 mg/kg).– After induction of anesthesia, patients received intraoper-

ative infusion according to their groups either remifen-

tanil (group I) or sodium nitroprusside (group II).

to assess eligibility and randomization.

306 E.M.K. Aboseif, S.M. Osman

3.1. In group I

Patients received 1 lg/kg remifentanil I.V. over 30–60 s., fol-lowed by a continuous infusion of 0.25–0.50 lg/kg/min untilsystolic blood pressure was brought within 80 mmHg, then

infusion rate was adapted to maintain hypotension at this level.

3.2. In group II

Patients received sodium nitroprusside as a continuous I.V.

infusion at a rate of 0.5 lg/kg/min until systolic blood pressurewas brought within 80 mmHg, then infusion rate was adaptedto maintain hypotension at this level.

Direct visual analysis of the surgical field was performedfrom starting surgery until the end of the surgery using thesix point scale.

In all cases, the surgeon infiltrated the submucosal tissue ofthe nose with 1:100.000 epinephrine to minimize blood loss.The surgeon was blinded to the hypotensive agent used, as well

as to the monitor recording the hemodynamic variables. Afterthe surgery, patients were recovered and were transferred tothe recovery area (PACU) for a continuous monitoring.

3.3. Statistical analysis

The required sample size has been calculated using theG*Power software version 3.1.7 (Universitat Dusseldorf,

Germany). The primary outcome measures were the time toonset of induced hypotension, time to target hypotension,and heart rate during hypotension. Secondary outcome

Table 1 Category scale of intraoperative surgical field

assessment.

0 No bleeding.

1 Slight bleeding – no suctioning required.

2 Slight bleeding – occasional suctioning required.

3 Slight bleeding – frequent suctioning required.

4 Moderate bleeding – frequent suctioning required. Bleeding

threatens the surgical field directly after suctioning removed.

5 Severe bleeding – constant suctioning required. Bleeding

appears faster than can be removed by suction. Surgical field

severely threatened and surgery is not possible.

Table 2 Patients’ characteristics in both study groups.

Variable Remifentanil group (n= 65)

Age (years) 30.0 (8.6)

Weight (kg) 70.9 (24.5)

Gender (M/F) 39/16

Baseline SBP (mmHg) 114 (19)

Baseline MAP (mmHg) 84 (9)

Baseline DBP (mmHg 69 (18)

Baseline heart rate (bpm) 73 (20)

Duration of anesthesia (min) 79 (32)

Data are presented as mean (SD).a Unpaired t test.b Pearson chi-squared test.c Welch test.

measures were the PaO2, PaCo2, and pH. It was estimated thata sample of 65 patients in either study group would have apower of 81% (type II error, 0.19) to detect a statistically sig-

nificant difference between the two study groups for a mediumeffect size of Cohen’s d = 0.5, which is equivalent to a differ-ence of 0.5 SD in the outcome measures. This difference was

chosen as it could be regarded as a clinically relevant differenceto seek in this pilot study. This calculation used a two-sidedunpaired t test and assumed a two-tailed type I error of 0.05.

Data were analyzed using IBMª SPSSª Statistics version22 (IBMª Corp., Armonk, NY, USA) and MedCalcª version13 (MedCalcª Software bvba, Ostend, Belgium). Continuousnumerical variables were presented as mean and SD, and inter-

group differences were compared using the independent-samples (unpaired) t test. The Welch test was used in place ofthe t test whenever equality of variance could not be assumed.

Categorical data were presented as number and percentage anddifferences were compared using the Pearson chi-squared test.

A two-sided p-value < 0.05 was considered statistically

significant.Our study is a non-equivalence study. So you are supposed

to use usual two-sided tests (see Table 1).

4. Results

Demographic data, duration of hypotension, duration of anes-

thesia and baseline hemodynamic data did not show any statis-tically significant difference among groups (Table 2). Infusionrate and the total dose of remifentanil and nitroprusside areshown in Table 3. There were no statistically significant differ-

ences between both groups regarding PaO2, PaCO2 and PHdata (Table 4).

Measurements of systolic, diastolic and mean arterial pres-

sure during the period of hypotension showed no significantdifferences between both groups. Heart rate during the periodsof hypotension was significantly lower in group (I) = remifen-

tanil group compared to group (2) = sodium nitroprussidegroup (p < 0.05).

Time to reach target systolic arterial blood pressure of

80 mmHg was significantly more in remifentanil group than innitroprusside group (P < 0.05) (Table 3).Therewere nopostop-erative complications in any group and all patients were dis-charged in the samedayof operation (after 6 hof operation end).

Nitroprusside group (n = 65) p-value

29.0 (10.9) 0.580a

68.2 (26.3) 0.555a

46/19 0.853b

115 (22) 0.797a

82 (12) 0.308c

65 (19) 0.300a

75 (20) 0.569a

82 (22) 0.557c

Table 3 Details of the induced hypotension in both study groups.

Variable Remifentanil group (n= 65) Nitroprusside group (n= 65) p-value

Time to onset of induced hypotension (s) 36 (21) 55 (15) <0.0001a

Time to target blood pressure (s) 68 (15) 109 (52) <0.0001a

Duration of induced hypotension (min) 47 (13) 48 (19) 0.948a

SBP during induced hypotension (mmHg) 81 (10) 80 (10) 0.585b

MAP during induced hypotension (mmHg) 57 (4) 56 (4) 0.174b

DBP during induced hypotension (mmHg) 48 (6) 48 (6) 0.864b

Heart rate during induced hypotension (bpm) 67 (25) 90 (25) <0.0001b

Total dose of hypotensive agent (mg) 1.6 (0.6) 5.4 (2.8) <0.0001a

Infusion rate of hypotensive agent (lg/kg/min) 0.31 (0.13) 0.98 (0.61) <0.0001a

Data are presented as mean (SD).a Welch test.b Unpaired t test.

Table 4 Change in arterial blood gas variables in both study groups.

ABG variable Time Remifentanil group (n= 65) Nitroprusside group (n= 65) p-value

PaO2 Baseline 93 (4) 92 (5) 0.171b

20 min 187 (33) 166 (40) 0.001a

40 min 173 (31) 180 (28) 0.187a

At PACU 141 (27) 123 (26) <0.0002a

PaCO2 Baseline 36 (2) 37 (2) 0.130a

20 min 32 (2) 41 (3) <0.0001b

40 min 34 (3) 40 (3) <0.0001a

At PACU 40 (3) 43 (3) <0.0001a

pH Baseline 7.37 (0.16) 7.39 (0.20) 0.552b

20 min 7.41 (0.10) 7.31 (0.06) <0.0001b

40 min 7.36 (0.27) 7.29 (0.09) 0.045b

At PACU 7.34 (0.26) 7.29 (0.09) 0.142b

Data are presented as mean (SD).a Welch test.b Unpaired t test.

Use of remifentanil in comparison with sodium nitroprusside for controlled hypotension 307

5. Discussion

In the present study, controlled hypotension is a well estab-

lished technique to decrease blood loss and improve surgicalvisibility during rhinoplasty and also many other operations.Many techniques have been successfully used in healthy

patients. In this study, we traced the advantage of usingRemifentanil to induce controlled hypotension rather thanthe traditional use of sodium nitroprusside. The remifentanilgroup showed statistically significant decrease time to reach

target systolic arterial blood pressure (86 ± 15) after(36 ± 12) versus sodium nitroprusside group (109 ± 55) after(55 ± 15).

These results were also reported by other studies such asPhilip [4] who used remifentanil to induce hypotensive in totalintravenous anesthesia and also Schuttler et al. [9] who used

remifentanil in comparison with alfentanil in patients undergo-ing major abdominal surgery.

Sodium nitroprusside also provided controlled hypotensionin the second group of patients in this study with advantages of

short duration of action, potency, and short time to reach thetarget hypotension, and this result was also reported byBoezzart and his colleagues [10], who also used nitroprusside

for inducing controlled hypotension for functional endoscopic

sinus surgery in comparison with esmolol and reported thatnitroprusside is a very effective drug in inducing controlled

hypotension.In the current study, we reported disadvantages of sodium

nitroprusside as reflex tachycardia which is not suitable in

patients with ischemic heart diseases, arrhythmia, tachyphy-laxis, and also rebound hypertension which is not suitablefor already hypertensive patients. These disadvantages were

also reported by Pinaud and his colleagues [11] who used nitro-prusside to induce hypotension in patients undergoing cran-iotomies. Nitroprusside also involved in inducing light butsignificant hypercapnia and acidosis as previously shown in

this study, and this was also reported by Tinker andMichenfelder [12] who did a full study on nitroprusside in1976.

Nitroprusside is a direct vasodilator acting directly on the

vascular smooth muscle causing generalized vasodilatation

and increase cardiac output, so increasing the blood flow to

the mucous membranes and to the capillaries these may lead

to increasing bleeding during surgery. This disadvantage of

nitroprusside was not reported in this study but, it is reported

by Chan et al. [13] who used nitroprusside to induce hypoten-

sion in patients undergoing anterior maxillary osteotomy

who revealed disadvantages of nitroprusside in the form of

308 E.M.K. Aboseif, S.M. Osman

degradation by light, cyanide toxicity and the need for invasiveblood pressure measurement.

6. Conclusion and recommendations

The present study showed that remifentanil infusion was inter-esting in providing controlled hypotension as well as dry surgi-

cal field in patients undergoing rhinoplasty with no need foradditional use of a potent hypotensive agent. Further studieson large scale are recommended to confirm these results.

Conflict of interest

We have no conflict of interest to declare.

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